A Master Non-Coding RNA Antagonizing Inflammation (AMANZI)

AMANZI is a 1000-nucleotide polyadenylated lncRNA transcribed within the locus controlling interleukin-1β (IL-1β) and interleukin-37 (IL-37)[1][2][3]. It is expressed in the nucleus, sharing its topological domain with both cytokine genes. AMANZI antagonizes inflammation by inhibiting IL-1β (a pro-inflammatory cytokine) and promoting IL-37 (an anti-inflammatory cytokine) expression. Genetic variants (notably SNP rs16944) within AMANZI can dramatically shift the balance of inflammatory versus anti-inflammatory responses, influencing individual susceptibility to infection, sepsis, and vaccine response. Mechanistically, the stability of AMANZI is increased by N6-methyladenosine methylation and subsequent YTH protein interaction, promoting its anti-inflammatory activity. Knockdown experiments indicate that AMANZI is a critical negative regulator in inflammatory circuits, making it a potential therapeutic target for inflammatory diseases and for modulating immune memory[1][2][3].

Epigenetic modulation of cytokine expression; Negative regulation of IL-1β (pro-inflammatory); Positive regulation of IL-37 (anti-inflammatory); m6A methylation stabilizes AMANZI and modulates its function.